The goal of this project is to examine the manner in which immunologic mechanisms may contribute to diseases of the nervous system. The cellular and humoral immune response to putative antigens and possible immunopathologic diseases such as multiple sclerosis (MS) are being studied. Included in these studies have been examinations of the immune response to viruses which can commonly infect the nervous system and which could be related to the induction of immunopathologic disease processes. In addition, the immune response to antigens of myelin such as myelin basic protein and proteolipid protein which may represent targets of immune-mediated diseases of myelin, has been studied. The emphasis in these studies has been on identifying differences in these immunologic responses which may occur in patients with diseases of the nervous system such as MS, as compared to healthy individuals. Particular attention has been given to examining the influence of genetic makeup on both the induction and effector phases of these immune responses. In particular, the role of HLA molecule genes and T-cell receptor investigated.